Human Heterosubtypic Immunity to Influenza A Virus: Evidence from Case Studies During the 1957 Pandemic

Abstract

Evaluation of: Epstein SL: Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature. J. Infect. Dis. 193, 49–53 (2006). Heterosubtypic immunity (HSI) to influenza A virus (IAV) occurs when some degree of protection to infection is afforded by prior infection with a different subtype of IAV (i.e., a strain with serologically non-crossreactive surface glycoproteins). The existence of HSI, although well-documented in mice, is uncertain in humans. In order to examine HSI in humans, Epstein retrieved data from the Cleveland Family Study, a study of 60 families with school-aged children. Importantly, these families were monitored for illness during 1947–1957, the end of which coincided with the Asian IAV pandemic caused by the introduction of the H2N2 strain into human populations. Culture-positive IAV infection rates were compared between adults and children. Interestingly, many more children became infected during the 1957 pandemic than adults (55 vs 17%). While previous IAV exposure during the 10-year study period provided protection against adult IAV infection in 1957 (only 5.6% were infected), no difference was observed in children previously infected with other subtypes of IAV (with 52% infected in 1957). Serum samples taken before the pandemic did not detectably interact with H2N2 glycoproteins, suggesting that factors other than virus-neutralizing antibodies provided HSI to adults. This re-evaluation of archived data provides an important demonstration of the possibility of HSI in humans. Improved knowledge of human HSI could lead to vaccines capable of limiting morbidity and mortality from future pandemic strains introduced into humans from animal reservoirs.